While a variety of agents are available for treatment of hypertension there, nevertheless, is a need for newer and improved antihypertensive agents to achieve better control of blood pressure in those subjects who do not respond satisfactorily or where drug associated side effects are seen.
This invention provides quinazoline compounds and pharmaceutically acceptable acid addition salts thereof having pharmacological properties making them particularly useful as antihypertensive agents. The quinazoline class of compounds of the instant invention structurally resemble the 2,4,6,7-tetrasubstituted quinazoline antihypertensive agents disclosed in U.S. Pat. No. 3,511,836. The compound "2-[4-(2-furoyl)-1-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline," known as prazosin, is representative of the quinazolines of U.S. Pat. No. 3,511,836 and has been studied in the clinic. Although prazosin is apparently an effective antihypertensive agent, it is not altogether free from alpha-adrenoreceptor blocking activity or from undesirable side effects such as postural dizziness and orthostatic hypotension; N. E. Pitts, Postgraduate Medicine, Prazosin, pp. 117-127 (November, 1975).
The compounds of the instant invention are generally substantially more potent than prazosin as antihypertensives while, at the same time, exhibiting appreciably less alpha-adrenoreceptor blocking activity. Also, compared to prazosin, the instant compounds are more potent phosphodiesterase inhibitors and exhibit greater selectivity for the enzyme operative on the cyclic guanosine monophosphate (cycle GMP) substrate.